This document prepares the clinician to discuss scientific data with the patient so they can make

an informed decision together.

What is this test for? This blood test detects mutations of the BRCA1 and BRCA2 genes. Individuals who carry these mutations have a higher

risk of developing breast and ovarian cancer.

What options are available to mutation carriers?1. Risk avoidance: increased physical activity and control of obesity, limiting alcohol consumption and dietary fat2. Cancer screening or surveillance3. Chemoprevention (e. g. tamoxifen, raloxifene)4. Risk-reducing surgery (mastectomy, salpingo-oophorectomy)

Who might consider being tested?1- Individuals who have a family history of:

known BRCA1/2 mutationovarian cancer in 2 or more relatives, at any ageovarian cancer at any age AND breast cancer under the age of 60 in 3 or more relativesbreast cancer in 3 or more relatives average age of onset before age 50male breast cancer AND ovarian cancer1

2- Individuals of French-Canadian or Eastern European ancestry who are diagnosed with breast cancer under the age of 50, are diagnosed with ovarian cancer at any age, or have a first-degree relative who was diagnosed with breast or ovarian cancer under the age of 50.1

3- Individuals of Ashkenazi Jewish heritage diagnosed with breast cancer under the age of 65 or ovarian cancer at any age or with a first-degree relative affected by breast or ovarian cancer under the age of 65.1

Individual risk for a BRCA1 or BRCA2 mutation can be calculated at https://www.myriadpro.com/brca-risk-calculator

Why do patient preferences matter when making this decision?

There are pros and cons to taking this testPROS: Individuals might benefit from knowing that they carry a mutation by taking steps to reduce their cancer risk.CONS: At least 12% of individuals who test negative for the mutation may still develop breast cancer and 1% may still

develop ovarian cancer. 2 From 35 to 90% of individuals with a BRCA1/2 gene mutation (depending on the mutation and of type of cancer) will not have breast or ovarian cancer, so screening could lead to an unnecessary invasive intervention that could have serious side effects (see graphs, page 2). 3

Both doing and not doing the test are acceptable options, so we propose that: the decision takes into account the patient’s values and preferences the clinician shares this decision with the patient

© Université Laval, 2012 all rights reserved See page 2 for the current state of knowledge

Probabilities of benefits and harms

Patient’s values and preferences

DECISION

Later

Yes No

Presenting the BRCA1/2 test to patients

The BRCA1/2 gene mutation test to evaluate the risks of breast and ovarian cancer

www.decisionbox.ulaval.ca

Harms of screening False reassuranceAt least 12% individuals without a BRCA1/2 mutation will develop breast cancer and 1% will develop ovarian cancer at some point in their lifetime.2 These individuals will have been falsely reassured. These proportions are greater in individuals with

familial history of cancer or of BRCA1/2 mutation.

False alarms (see graphs below)*35-55% of BRCA1/2 mutation carriers will never develop breast cancer in their lifetime, and 60-90% of BRCA1/2 mutation carriers will never develop ovarian cancer.3

OverdiagnosisWomen identified as mutation carriers may use chemoprevention to reduce their risks. 10% will undergo a prophylactic bilateral mastectomy and 40% will undergo a prophylactic salpingo-oophorectomy.5 These interventions reduce cancer risks but some treated women will still have cancer.

AnxietyPositive test results disclose genetic information about individuals and family members. This may create anxiety for individuals and tension within families.

ConfidentialityIndividuals known to be mutation carriers may experience discrimination by employers or Insurance companies.

Benefits of screening ReassuranceFor each 1000 individuals screened, 985 (98.5%) will not have a mutation and can adhere to the general population screening guidelines. These individuals will be reassured.4

Reduce cancer risksFor each 1000 individuals screened, 15 (1.5%) will have a mutation detected. These individuals can choose to take steps to reduce their risks of having breast and/or ovarian cancer.4

*Confidence in the results: Moderate The reported effect is inconsistent among trials. The study findings presented here are founded on a pooled analysis of 22 studies conducted in 12 countries with individuals carrying a broad spectrum of mutations.3

© Université Laval, 2012 all rights reserved

State of knowledge – October 2011Selection of best available studies

BRCA1/2

Number of individuals with BRCA1/2 mutations found for each 1000 screened.4

Family history

without breast cancer < 50 years old or ovarian cancer in any relative

with breast cancer < 50 years old and/or ovarian cancer in at least a relative

General population

15

70

Personal history of cancer ↕

260

575

Ashkenazi Ancestry

85

230

↕ Breast cancer < 50 years old, and ovarian cancer at any age

Breast Cancer 3

55% will not developbreast cancer

35% will not develop breast

cancer

65% will developbreast cancer

45% will develop breast cancer

Individuals with a BRCA1 mutation

Individuals with a BRCA2 mutation

Ovarian Cancer 3

90% will not developovarian cancer

60% will not developovarian cancer

40% will developovarian cancer

10% will developovarian cancer

Individuals with a BRCA1 mutation

Individuals with a BRCA2 mutation

DECISIONBOX

Questions to identify the patient's decision making needs: Do you have any questions about the benefits and harms of each option? Which benefits and harms matter most to you? Do you feel sure about the best choice for you? Who will support and advise you in making a choice?

6

6

Study descriptions and references: 1. McGill Cancer Genetics Program 2006,

http://www.mcgill.ca/files/cancergenetics/ReferralGuidelinesBreastOvarian. 2. National Cancer Institute 2010, http://seer.cancer.gov/faststats. 3. Antoniou et al. Am J Hum Genet 2003, 72(5), 1117-1130. Study Design:

Systematic review of 22 case series studies in 12 countries. Participants: 8,000 individuals with breast/ovarian cancer (98% women, 2% men) unselected for family history. Of the 8000, 6% had a BRCA1/2 mutation. Methods: Cancer occurrence probabilities estimated with computer simulations.

4. Myriad Genetic Laboratories Inc. 2010. Study Design: Registry from a private molecular diagnostic company. Participants: 162,000 individuals from the U.S.

who requested to be tested for the BRCA1/2 gene mutation.5. Domchek et al. JAMA 2010, 304(9), 967-975. Study Design: Prospective

multi-center cohort study assessing the relationship between risk-reducing mastectomy and risk-reducing salpingo-oophorectomy and cancer outcomes. Participants: 2,500 women with BRCA1/2 mutations from 22 clinical and genetics centres in North America and Europe. Length of follow-up: 4 years.

6. Genetikit Research Team. Gene Messenger 2010, http://www.cfp.ca/content/54/12/1691/suppl/DC1

www.decisionbox.ulaval.ca

http://www.decisionbox.ulaval.ca/index.php?id=821&L=2http://www.decisionbox.ulaval.ca/index.php?id=836&L=2

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